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Page 4 of 6 Carvalho et al. Hepatoma Res 2020;6:6 I http://dx.doi.org/10.20517/2394-5079.2019.027

[23]
A European study by Bamia et al. evaluated more than 521,000 individuals between 1992 and 2000 in
10 European countries to look for the etiologic factors of cancers and other chronic diseases. Dietary data,
including coffee intake, were obtained through previously validated questionnaires. After 11 years of follow-
up, 133 men and 68 women were diagnosed with HCC, and the results showed an average consumption
of 354 mL per day of coffee among men and 290 mL of coffee per day among women. Seven percent of
participants did not drink coffee. There was an inverse association between coffee consumption and the risk
of HCC, and coffee consumption proved to be a liver protective factor in all groups. The higher the coffee
intake, the lower the risk of liver carcinogenesis, with statistically significant results.

[24]
Aleksandrova et al. analyzed the data obtained from the European Prospective Investigation into Cancer
and Nutrition, a study conducted from 1992 to 2000 on more than 520,000 individuals that aimed to
establish a relationship between protection from coffee consumption and the risk of HCC in addition to
serum markers of inflammation. Coffee consumption showed an inverse association with the development
of HCC, with 20% more coffee consumers having an approximately 70% lower chance of HCC. Conjugate
analysis of serum markers and coffee consumption showed a statistically significant reduction in all markers
of liver inflammation (IL-6, glutamate dehydrogenase, alanine transaminase, aspartate transaminase, GGT,
alkaline phosphatase, total bilirubin, and alpha-fetoprotein). All of these markers were directly associated
with a higher risk of hepatocellular carcinoma.

IMPACT OF COFFEE CONSUMPTION ON HCC MORTALITY
[25]
Kurozawa et al. , through a prospective cohort study from 1988 to 1999, evaluated the impact of coffee
consumption on HCC mortality in a total of 110,792 individuals. In HCC mortality analyses, consumers
of less than one cup of coffee per day had a lower risk of death from HCC, and this risk was even lower in
consumers of at least one cup of coffee per day, showing a quantitative association between consumption and
mortality from hepatocellular carcinoma. In subjects reporting a history of liver disease, coffee consumption
was an even more prominent protective factor when compared to those who did not drink coffee or drinkers
with no history of liver disease.

COFFEE CONSUMPTION AND RECURRENCE OF HCC AFTER LIVER TRANSPLANTATION
Orthotropic liver transplantation (OLT) is the therapeutic option with the most favorable outcome as it
offers radical removal of the tumor and eliminates underlying chronic liver disease in selected patients or
those with early-stage HCC. However, recurrence of HCC after OLT remains a serious problem with up
to 20% risk. Recent studies have identified several risk factors for HCC recurrence, such as biological and
[26]
radiological progression on the waiting list, number of tumor nodules, and poor differentiation . However,
the mechanisms are still poorly understood, and potential post-OLT strategies to prevent HCC recurrence
are still needed.

Recent studies show that caffeinated coffee consumption is associated with a reduced risk of HCC recurrence
and longer survival following OLT. Experimental data suggest that such benefits of coffee are associated, at
least in part, with the caffeine antagonist activity in promoting adenosine receptor-mediated growth by HCC
[27]
cell effects .

CONCLUSION
The present review suggests that a daily habit of drinking coffee seems to protect against the development of
HCC. The mechanisms may induce recurrent cycles of cell damage, repair, and regeneration in hepatocytes,
leading to the formation of dysplastic nodular lesions, which are precursor lesions of HCC. Genetic and
epigenetic changes may also influence HCC development. Caffeine is only one of the components of coffee;
however, it appears to play a central role in protecting against the development of chronic liver disease and